Pancreatic exocrine insufficiency is a major consequence of pancreatic diseases (e.g., chronic pancreatitis, cystic fibrosis, severe acute necrotizing pancreatitis, and pancreatic cancer), extrapancreatic diseases such as celiac disease and Crohn's disease, and gastrointestinal and pancreatic surgical resection. Replacement of pancreatic exocrine function is important to avoid malnutrition-related morbidity and mortality. One therapy for pancreatic exocrine insufficiency is the oral administration of pancreatic enzymes to provide the duodenal lumen with sufficient active lipase at the time of gastric emptying of nutrients. Typically these enzymes are administered in the form of enteric-coated mini-microspheres to avoid acid-mediated lipase inactivation and to ensure gastric emptying of enzymes in parallel with nutrients.
Pancreatic enzyme preparations (PEPs) obtained from animal sources have been used in various forms over the past seventy years to partially remedy enzyme deficiency in patients suffering from various pancreatic enzyme deficiency and digestive disorders. PEPs typically contain a combination of at least three enzymes including: lipase, protease, and amylase, which are important in the digestion of fats, protein and sugars. One PEP known as pancrelipase is commercially available in the form of enteric coated capsules which contain up to 35,000 USP units/capsule of pancrelipase (e.g., PANCRECARB® (Digestive Care, Inc.), ULTRASE® (Axcan Scandiphann Inc.), PANCREASE™ (McNeil Pharmaceutical), COTAZYME® (Organon USA, Inc.), and CREON® (Solvay Pharmaceuticals, Inc.)).
Since these enzymes are isolated from animal sources, they are susceptible to being contaminated with genomic copies of porcine parvovirus (PPV). While there are a number of known methods for determining the viral infectivity and viral content of animal derived products, they have many drawbacks. For instance, ultracentrifugation and many extraction methods have limited reproducibility and low detection limits, and cannot be readily scaled up for commercial use. Many of these limitations are due to the nature of animal derived products. The particularly complex nature of PEPs is a major cause for the difficulty in precisely and accurately determining their PPV content.
Therefore, there is a need for reproducible, precise, and efficient methods for determining the PPV content and PPV infectivity of PEPs, such as pancrelipase.